November 20 – For men who have a low sperm count or no sperm at all, diagnosis of the problem often requires biopsy of one or sometime both of the testicles and sometimes additional surgery that can last for many hours.

That could change in the near future, thanks to a simple semen test developed at Mount Sinai Hospital that is proving effective in pin-pointing the specific cause of infertility in individual men.

Dr. Keith Jarvi and Dr. Andrei Drabovich

“Testing a semen sample could be done in the doctor’s office. It’s noninvasive and so much easier for the patient than is surgery,” says Dr. Keith Jarvi, head of urology at Mount Sinai Hospital. “The test will also be more conclusive in giving men and their partners the answers they need in order to understand their choices and decide on next steps for creating a family,” he says. At Mount Sinai, Dr. Jarvi is Director of the Murray Koffler Urologic Wellness Centre, Head of Urology, and Associate Scientist at the Lunenfeld-Tanenbaum Research Institute. He is a Professor of Surgery at University of Toronto.

Dr. Jarvi and fellow researchers at the Lunenfeld-Tanenbaum Research Institute publish their findings today in Science Translational Medicine.

Alternate to three-hour surgery

Up to seven per cent of men, or 500,000 Canadian men, are infertile. In about 20 per cent of men with no sperm or low sperm counts, the cause could be either an obstruction that prevents healthy sperm from entering the semen prior to ejaculation, or a lack of sperm production (non-obstructive azoospermia). There is no simple test currently available that shows whether the infertile man has some healthy sperm or not.

Men who have an obstruction or are producing just a few sperm may have the option of having their healthy sperm retrieved surgically from the testicle. “We’re literally opening up a testicle in order to hunt for sperm in dozens of tiny ducts. It can take two or three hours, but if we don’t find sperm that doesn’t mean it isn’t hidden in another duct. For that reason, some men go through this surgery more than once, and still don’t get a conclusive answer about whether or not they have some healthy sperm that we could retrieve,” he says.

Sperm retrieval for use in in vitro fertilization is an option for these couples. “It’s important for men and their partners to know whether IVF is a possibility for them or not,” says Dr. Jarvi.

Analyzing 18 proteins in semen

Remarkably, the new semen test described in this paper identifies both the obstructive and non-obstructive causes of an absence of sperm in semen. More than 3,000 proteins are found in human semen. “Of these, we identified 18 proteins whose concentration tells us that something may have gone wrong in the male reproductive system,” says lead author Dr. Andrei Drabovich, a post-doctoral fellow at the Lunenfeld-Tanenbaum. “That’s true whether the problem is caused by an obstruction in the tubes that take the sperm out from the testicles, or the problem is one of producing sperm of poor quality, he adds.

Using mass spectrometry, the research team fine-tuned an analysis of semen that shows exactly where the problem lies in an individual semen sample. “With this study, we showed how the test works in the research lab. Now we are moving ahead on developing a simple and inexpensive clinical lab test that can be added to any physician’s toolbox,” Dr. Drabovich says.

Getting regulatory approval will be the next step, adds Dr. Jarvi. “We’re one to two years away from rolling the test out to physicians’ offices around the world, but as a urologist and male fertility specialist I’m awfully glad to know that our test shows such promise and is well on its way.”

Another potential use of this research is the reverse of treating men with infertility, and that is developing a male contraceptive. “Among the proteins found in semen there is one that turns out to be essential for normal fertilization. If a semen sample lacks this protein it means that fertilization is not possible. If we can find a way to block that protein in the first place we may have a male contraceptive,” adds Dr. Drabovich.

The paper is published on-line in Science Translational Medicine on November 20. The title is “Differential diagnosis of azoospermia with proteomic biomarkers ECM1 and TEX101 quantified in seminal plasma.” The research was funded by Canadian Institutes of Health Research, Physicians’ Services Incorporated grants, and the Mount Sinai Hospital Foundation Norm Hollend post-doctoral fellowships.